Calcium Release from Stores Inhibits GIRK

Highlights

• mGluR-mediated calcium release from stores inhibits GIRK currents

• GIRK inhibition does not require G_q or G_i receptor activation

• GABA_BR IPSCs are inhibited when calcium is released 1–5 s before stimulation

• Inhibitors of PKC, PLC, PLA₂, and calmodulin had no effect on GIRK inhibition

Summary

Synaptic transmission is mediated by ionotropic and metabotropic receptors that together regulate the rate and pattern of action potential firing. Metabotropic receptors can activate ion channels and modulate other receptors and channels. The present paper examines the interaction between group 1 mGluR-mediated calcium release from stores and GABA_B/D2-mediated GIRK currents in rat dopamine neurons of the Substantia Nigra. Transient activation of mGluRs decreased the GIRK current evoked by GABA_B and D2 receptors, although less efficaciously for D2. The mGluR-induced inhibition of GIRK current peaked in 1 s and recovered to baseline after 5 s. The inhibition was dependent on release of calcium from stores, was larger for transient than for tonic currents, and was unaffected by inhibitors of PLC, PKC, PLA₂, or calmodulin. This inhibition of GABA_B IPSCs through release of calcium from stores is a postsynaptic mechanism that may broadly reduce GIRK-dependent inhibition of many central neurons.